title: Cortical murine neurons lacking the neurofilament light chain protein have an attenuated response to injury in vitro.
abstract: Neurofilaments (NFs) have been proposed to have a significant role in attempted axonal regeneration following a variety of forms of injury. The NF triplet proteins of the central nervous system are comprised of light (NF-L), medium (NF-M) and heavy (NF-H) chains and are part of the type IV intermediate filament family. We sought to define the role of NF-L in the neuronal response to trauma and regeneration by examining the effect of total absence of the NF-L protein on neuronal maturation and response to axotomy. This study utilized an in vitro model comprising relatively mature cortical murine neurons derived from either wild-type embryonic (E15) mice or mice with a genetic knockout of NF-L (NF-L KO). Whilst NF-L KO neurons developed to relative maturity at a comparable rate to wild-type control neurons, NF-L KO neurons demonstrated relatively increased expression of α-internexin and decreased expression of NF-M. Further, we demonstrate that α-internexin co-immunoprecipitates with the NF binding protein NDel1 in NFL-KO cortical neurons in vitro. Following localized axotomy, NF-L KO neurons demonstrated reduced amyloid precursor protein accumulation in damaged neurites as well as a significant reduction in the number of axons regenerating (4.79+/-0.58 sprouts) in comparison to control preparations (10.47+/-1.11 sprouts) (p<0.05). These studies indicate that NFs comprising NF-L have a dynamic role in the reactive and regenerative changes in axons following injury.
authors.affiliation: 1 Menzies Research Institute Tasmania, School of Medicine, University of Tasmania , Tasmania, Australia .
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Blizzard
authors.forename: Anna E
authors.initials: AE
authors.lastname: King
authors.forename: James
authors.initials: J
authors.lastname: Vickers
authors.forename: Tracey
authors.initials: T
authors.lastname: Dickson
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D019771:Axotomy; D002352:Carrier Proteins / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D004622:Embryo, Mammalian; D007381:Intermediate Filament Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016900:Neurofilament Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D007381:Intermediate Filament Proteins; C486015:Ndel1 protein, mouse; D016900:Neurofilament Proteins; C046643:alpha-internexin; C044882:neurofilament protein L; C061195:neurofilament protein M